We have recently demonstrated a striking enhancement of hepatoma induction by several chemicals in rats fed a diet devoid of choline. Several lines of experimental observations lend support to the notion that enhanced liver carcinogenesis by this dietary modification may be mediated through the promoting effects of a choline-devoid (CD) diet. Using the initiation-promotion scheme of liver carcinogenesis, we will attempt to define more clearly the role of a CD diet on promotion of carcinogenesis. Cellular analysis of progression of foci of initiated hepatocytes to hepatoma, under the influence of a CD diet or a CS diet, will be undertaken to determine their reversibility and possible phenotypic alterations which may occur during the course of the progression. Selected aspects of the mechanism of tumor promotion in the liver by a CD diet will be investigated, including the effects of the diet on liver cell proliferation and on liver cell differentiation. It is hoped that these studies will lay a foundation for future studies concerning the cellular and biochemical basis of the modification of the carcinogenic process induced by other dietary components.